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J T Kemshead

Publications and source records attributed to J T Kemshead.

At least 109 records · Page 6Linked to original sources
PubMed1987

Monoclonal antibodies and magnetic microspheres for the depletion of leukaemic cells from bone marrow harvested for autologous transplantation.

The use of a panel of monoclonal antibodies and anti-mouse immunoglobulin-coated microspheres is described for the depletion of leukaemic blasts from bone marrow. Marrow treated in this way rapidly reconstitutes haemopoietic function after high-dose consolidation chemoradiotherapy. The recovery of cells from bone marrow is similar but not identical to results obtained on removal of neuroblasts from marrow to be used for autologous transplant. This is probably a reflection of the cross-reactivity of 'anti-leukaemic' antibodies with a variety of haemopoietic progenitor cells. The study described here demonstrates the feasibility of using this method to purge leukaemic cells from bone marrow. A much larger randomised study between patients receiving either purged or non-purged bone marrow would be necessary to validate the need to remove small numbers of tumour cells from bone marrow.

Antibodies, Monoclonal↗
PubMed1987

Therapeutic application of radiolabeled monoclonal antibody UJ13A in children with disseminated neuroblastoma.

Dosimetric data from UJ13A scanning studies using 131I are presented for children with stage IV neuroblastoma and primary brain tumor. The data demonstrate a large variation among patients in dose delivery to vulnerable organs and tumors. Against this background, a phase I toxicity study is under way with escalating amounts of conjugate administered to patients who have stage IV neuroblastoma. Major toxicity has been confined to bone marrow aplasia and necessitates bone marrow harvest prior to therapy. Specific problems encountered include altered kinetics during therapy following tracer studies and adequate dose delivery in large tumor masses.

Antibodies, Monoclonal↗
PubMed1986

Radioimmunolocalization of human brain tumours: biodistribution of radiolabelled monoclonal antibody UJ13A.

Monoclonal antibody UJ13A, radiolabelled with 131I, was intravenously administered to patients with primary brain tumours. The antigen recognised by UJ13A is present on most neuroectodermally derived tissue. The ratio of uptake in tumour to normal brain, assessed by scintigraphy, improved with time. Maximal tumour uptake occurred between 4 and 48 h. Dynamic and static scintigrams indicated some early sequestration of radiolabelled antibody by the liver. Tumours were surgically resected in seven patients at various intervals after antibody administration showing tissue to blood ratios increasing with time in all parts of the lesion (viable and necrotic tumour, cyst fluid), and in normal brain. The highest tissue to blood ratio in viable tumour was 5.1 at 16 days after injection. In tissues resected 2-3 days after injection there was relatively greater uptake in the viable tumour compared to necrotic tumour and cyst fluid. In contrast, tissues resected later (6-16 days) showed greater uptake in ischaemic tissue than viable tumour, suggesting diffusion was an important factor influencing tumour uptake. The amount of radioactivity per gram of tumour tissue was less than 0.005% of the injected dose. Future studies are needed using different antibodies, antibody fragments and additional methods of optimising delivery.

Antibodies, Monoclonal↗
PubMed1986

Phenotypic analysis of cultured melanoma cells. Expression of cytokeratin-type intermediate filaments by the M5 human melanoma cell line.

Expression of intermediate filament (IF) isotypes was studied in six human and two murine melanoma cell lines. With one exception, these lines expressed IFs only of the vimentin type; neurofilament peptides, desmin and GFAP were not detected. However, the M5 human melanoma line also expressed extensive cytokeratin tonofilament arrays, as visualized by immunofluorescence with a panel of eleven monoclonal antibodies and hetero-antisera to cytokeratins; only the keratin 19-specific antibody BA16 did not react. By 2 D gel electrophoresis, five major keratin peptides were detected (keratins 7, 8, 13, 17 and 18), and an additional 57 kD peptide was detected on immunoblots with several antikeratin antibodies. Also observed in M5 cells was focal collapse of tonofilament arrays in mitotic cells. All the melanoma lines tested were positive for S100; M5 and two other cell lines were also positive for the 220-240 kD neuroectoderm-associated cell-surface differentiation antigen defined by monoclonal antibody UJ 127:11. In all the melanoma cell lines, secretion of extracellular matrix proteins (fibronectin, laminin and collagen type IV) was sparse or absent, and all were negative for the epithelial cell markers HMG-1 and HMG-2. Co-expression of keratin and vimentin by a melanoma cell line is discussed in the light of recent controversy concerning expression of cytokeratins by other neoplasms of putative neuroectodermal origins.

Antibodies, Monoclonal↗
PubMed1986

Comparative studies between a new human rhabdomyosarcoma cell line, JR-1 and its tumour of origin.

A new human embryonal rhabdomyosarcoma cell line, designated JR-1, is described that closely resembles the tumour from which it was derived. Comparative studies, by light and electron microscopy reveal morphological features such as myofibre formation, that are concordant with embryonal rhabdomyosarcoma. Immunohistological investigations using a panel of monoclonal antibodies indicate that the cell surface antigen profile of the JR-1 cell line is similar to other embryonal rhabdomyosarcomas. In addition the cell line expresses the cytoplasmic intermediate filament protein desmin, only found in cells of rhabdoid origin. Karyotyping JR-1 shows the cells to contain variable numbers of chromosomes (range 44-100). DNA flow cytometry indicates that cells have an DNA content which is approximately twice normal. The JR-1 cell line has a doubling time of 29 h in culture and, in common with several other human cell lines, produces xenografts in nude mice within 6 weeks of inoculation. With detailed studies on the original tumour and the JR-1 cell line, the latter should prove an excellent model system for investigating the biology of rhabdomyosarcoma.

Animals↗
PubMed1986

Magnetic microspheres and monoclonal antibodies for the depletion of neuroblastoma cells from bone marrow: experiences, improvements and observations.

Improvements to the original procedure of using a panel of monoclonal antibodies and magnetic microspheres for the depletion of tumour cells from bone marrow are described. These include a completely disposable system for the magnetic depletion of tumour cells coated with magnetic microspheres. Properties of a new series of microspheres are compared with the old M330 beads in their ability to deplete neuroblasts from both model systems and 50 bone marrows harvested from Stage IV neuroblastoma patients. Using human neuroblastoma cell lines labelled with the DNA intercalating, Hoechst dye 33342 a 5% tumour contamination can routinely be removed from 5 X 10(6) - 5 X 10(7) nucleated cells. Analysis of the 50 purged marrows revealed that 10 were visibly contaminated with tumour (by conventional cytology and immunological procedures). In all but one case, tumour cells were removed. In this instance the tumour:bead ratio fell to 1:4 indicating the importance of maintaining a sufficient number of beads in the system. Red cell contamination of marrow was also kept extremely low so preventing possible physical blockade of bead:tumour cell interaction. Marrow engraftment was rapid in this group, apart from patients who had been exposed to high doses of alkylating agents prior to autografting.

Antibodies, Monoclonal↗
PubMed1986

131-I coupled to monoclonal antibodies as therapeutic agents for neuroectodermally derived tumors: fact or fiction?

It has been suggested that monoclonal antibodies may be useful in targeting cytotoxic compounds to tumor cells. We have explored their use in targeting 131-I to highly radiosensitive primitive neural tumors such as neuroblastoma and pineoblastomas. Two routes of administration have been employed, intravenous and intrathecal. Our current experience in using radiolabelled antibodies is described, indicating toxicities seen and any therapeutic benefit observed. The results of the study suggest that if targeted radiation has a role in the treatment of these malignancies, it will be restricted to the eradication of small tumor masses from the body.

Animals↗
PubMed1986

Identical expression of cell surface membrane antigens on two parent and eighteen cloned cell lines derived from two different neuroblastoma metastases of the same patient.

Two neuroblastoma cell lines established from tumor tissue taken from one individual are described. The first of these was established from a bone marrow aspirate (RT-BM) and the other from a right axillary lymph node (RT-LN) of a 1-yr 2-mo-old patient with Stage IV disease. The original lines were cloned in soft agar to yield six clones of the bone marrow-derived line (RT-BM 1-6) and 12 of the lymph node line (RT-LN 1-12). Chromosomal analysis of the original lines and clones showed they all have either identical or very similar karyotypes, with a deletion of chromosome 1p. Transmission electron microscopy indicates all contain neurosecretory (dense core) granules and neurotubules. In addition catecholamine metabolites of dopamine and noradrenaline have been identified. Different growth characteristics of the lymph node and bone marrow lines have been identified. RT-LN lines grow in a single cell layer with neurite processes, whereas bone marrow-derived lines form focal aggregates with neurite processes. In addition the colony-plating efficiency of the lymph node-derived lines is higher than those derived from bone marrow. Comparison of the cell surface antigen profile of the original tumor tissue, parent lines, and clones demonstrates they all bind seven of a panel of nine monoclonal antibodies. The expression of these antigens has remained stable in vitro for 25 passages undertaken over a 2-yr period. The definition of antigens that are expressed on the membranes of neuroblastoma cells in a stable form can aid in the differential diagnosis of neuroblastoma from other "small round cell tumors of childhood" and hopefully contribute to a greater understanding of the biology of this highly malignant tumor.

Antibodies, Monoclonal↗
PubMed1985

Therapeutic application of a radiolabelled monoclonal antibody in nude mice xenografted with human neuroblastoma: tumoricidal effects and distribution studies.

Monoclonal antibody UJ13A radiolabelled with isotopes of iodine has been shown to selectively localize to human neuroblastoma xenografts. When 131I-UJ13A conjugates were given to nude mice at high doses (100-150 microCi), tumours temporarily disappeared, only to regrow. No selection for neuroblastoma cells that were UJ13A - negative was observed. Distribution studies on mice receiving radiolabelled UJ13A demonstrated the antibody is rapidly lost from the blood of animals. This cannot be accounted for by selective uptake into xenografts or any other mouse organ examined. We concluded there is a rapid equilibration of isotope between intra- and extravascular spaces in the animal. The rapid, biphasic loss of UJ13A from the blood of mice may explain why so little injected antibody can target to the human tumour xenografts.

Animals↗
PubMed1985

Magnetic separation techniques: their application to medicine.

Whilst separation techniques relying on gravitational forces have become relatively sophisticated in their application to biology the same is not true for magnetic separation procedures. The use of the latter has been limited to the few cells which contain paramagnetic iron. However with the development of several different types of magnetic particles and selective delivery system (e.g. monoclonal antibodies) the use of magnetic separation techniques is growing rapidly. This review describes the different types of particles currently available, the magnetic separation technique applied to the different magnetic compounds and illustrates major uses to which magnetic separation procedures are currently applied in the area of biology and medicine.

Animals↗
PubMed1985

The role of monoclonal antibodies in brain tumour diagnosis and cerebrospinal fluid (CSF) cytology.

This paper reviews the diagnostic role of monoclonal antibody immunohistochemistry in a series of 189 brain tumour biopsies and 22 cases of neoplastic meningitis. The diagnostic monoclonal antibody panel, which includes markers for glial, neural, epithelial and lymphoid differentiation antigens, was used to test a wide variety of cerebral and spinal tumours by indirect immunofluorescence and immunoperoxidase techniques on unfixed frozen sections. Gliomas, meningiomas, schwannomas, medulloblastomas, choroid plexus tumours, cerebral lymphomas and metastatic carcinomas could all be reliably differentiated by means of their characteristic antigenics profiles, as defined by their patterns of reactivity with the antibody panel. Confident diagnosis was possible even in very poorly differentiated tumours and in biopsies distorted by surgical squeeze artefact, where paucity of morphological clues made diagnosis by conventional histological methods difficult or impossible. It was estimated that use of the antibody panel was responsible for, or made a significant contribution towards the final diagnosis in approximately 20% of cases. The monoclonal reagents were also found to be of great value in the detection and characterisation of neoplastic cells in CSF specimens from patients with malignant meningitis. Malignant cells were detected in 73% of cases and characterised in 16% of cases by routine cytological techniques. Employing monoclonal immunocytology however, these figures were improved to 95% and 95% respectively. Our findings suggest that patients with neoplastic meningitis can be spared prolonged investigation and inappropriate management by the early detection and characterisation of malignant cells in CSF using panels of monoclonal antibodies.

Antibodies, Monoclonal↗
PubMed1985

Immunohistological diagnosis of central nervous system tumours using a monoclonal antibody panel.

A panel of seven monoclonal antibodies has been used to characterise 164 cerebral and spinal tumours. These reagents have enabled rapid and accurate diagnosis of tumours to be made, particularly in cases where standard techniques have proved equivocal. On the basis of characteristic antigenic profiles of tumours, it has been possible to distinguish between gliomas, meningiomas, schwannomas, medulloblastomas, neuroblastomas, choroid plexus tumours, various metastatic deposits, and primary brain lymphomas. The reagents used in the study comprise antibodies binding to (a) most neuroectodermally derived tissues and tumours (UJ13A), (b) fetal brain and tumours of neuroblastic origin (UJ181.4), (c) schwannomas, normal and neoplastic neurones (UJ127.11), (d) glial cells (FD19), (e) epithelial cells (LE61), and (f) leucocytes (2D1). Some reagents, such as antibody A2B5, were less effective as diagnostic markers than originally suggested by previously described specificity. This monoclonal antibody reacted with both neuroectodermal and epithelial derived tumours. The panel of monoclonal antibodies was most useful in the diagnosis of tumours composed of small round cells, particularly lymphoma and neuroblastoma, but the pattern of reactivities allowed most of the central nervous system tumours to be accurately classified. This approach was a valuable adjunct to conventional histological techniques in about 20% of the cases examined.

Aged↗